NCT03117998已完成2 期
A Randomized, Placebo-controlled, Double-blind Study to Evaluate the Efficacy, Safety, and Pharmacodynamics of Multiple Doses of REMD-477 in Subjects With Type 1 Diabetes Mellitus
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 154
- 试验地点
- 11
- 主要终点
- Change in Average Daily Total Insulin Use
研究概览
简要总结
This is a randomized, placebo-controlled, double-blind study to evaluate the efficacy, safety, and pharmacodynamics (PD) of multiple doses of REMD-477 in subjects who have Type 1 diabetes and are currently receiving insulin treatment. This study will determine whether REMD-477 can decrease daily insulin requirements and improve glycemic control after 12 weeks of treatment in subjects diagnosed with Type 1 diabetes with fasting C-peptide < 0.7 ng/mL at Screening.
The study will be conducted at multiple sites in the United States. Approximately 150 subjects with type 1 diabetes on stable doses of insulin will be randomized in a 1:1:1 fashion into one of three treatment groups.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women between the ages of 18 and 65 years old, inclusive, at the time of screening;
- •Females of non-child bearing potential must be ≥1 year post-menopausal (confirmed by a serum follicle-stimulating hormone (FSH) levels ≥ 40 IU/mL) or documented as being surgically sterile. Females of child bearing potential must agree to use two methods of contraception;
- •Male subjects must be willing to use clinically acceptable method of contraception during the entire study;
- •Body mass index between 18.5 and 32 kg/m2, inclusive, at screening;
- •Diagnosed with Type 1 diabetes, based on clinical history or as defined by the current American Diabetes Association (ADA) criteria;
- •HbA1c > 7% and < 10 % at screening;
- •Fasting C-peptide < 0.7 ng/mL;
- •Treatment with a stable insulin regimen for at least 8 weeks before screening with multiple daily insulin (MDI) injections or continue subcutaneous insulin infusion (CSII)
- •Willing to use continuous CGM system (e.g. DexCom) throughout the study;
- •Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 1.5x upper limit of normal (ULN) at screening;
- •Able to provide written informed consent approved by an Institutional Review Board (IRB).
排除标准
- •History or evidence of clinically-significant disorder or condition that, in the opinion of the Investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion;
- •Significant organ system dysfunction (e.g., clinically significant pulmonary or cardiovascular disease, anemia [Hemoglobin < 10.0 g/dL], known hemoglobinopathies, and renal dysfunction [eGFR < 60 ml/min]);
- •Any severe symptomatic hypoglycemic event associated with a seizure or requiring help from other people or medical facility in the past 6 months;
- •Myocardial infarction, unstable angina, revascularization procedure, or cerebrovascular accident ≤12 weeks before screening;
- •History of New York Heart Association Functional Classification III-IV cardiac disease;
- •Current or recent (within 1 month of screening) use of diabetes medications other than insulin - subjects on an SGLT2 inhibitor should be discontinue the SGLT2 inhibitor during the Screening Period, at least 2 weeks prior to the start of the Lead-in Period;
- •Use of steroids and/or other prescribed or over-the-counter medications that are known to affect the outcome measures in this study or known to influence glucose metabolism;
- •Smokes > 10 cigarettes/day, and/or is unwilling to abstain from smoking during admission periods;
- •Known sensitivity to mammalian-derived drug preparations, recombinant protein-based drugs or to humanized or human antibodies;
- •History of illicit drug use or alcohol abuse within the last 6 months or a positive drug urine test result at screening;
- •History of pancreatitis, pancreatic neuroendocrine tumors or multiple endocrine neoplasia (MEN) or family history of MEN;
- •History of pheochromocytoma, or family history of familial pheochromocytoma;
- •Known or suspected susceptibility to infectious disease (e.g. taking immunosuppressive agents or has a documented inherited or acquired immunodeficiency);
- •Known history of positive for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HbsAg), or hepatitis C antibodies (HepC Ab);
- •Participation in an investigational drug or device trial within 30 days of screening or within 5 times the half-life of the investigational agent in the other clinical study, if known, whichever period is longer;
- •Blood donor or blood loss > 500 mL within 30 days of Day 1;
- •Women who are pregnant or lactating/breastfeeding;
- •Unable or unwilling to follow the study protocol or who are non-compliant with screening appointments or study visits;
- •Any other condition(s) that might reduce the chance of obtaining study data, or that might cause safety concerns, or that might compromise the ability to give truly informed consent
- •Other inclusion and exclusion criteria may apply.
研究组 & 干预措施
35 mg REMD-477
Experimental
Administered as a repeated subcutaneous (SC) doses in subjects with Type 1 Diabetes
干预措施: REMD-477 (Biological)
Matching placebo
Placebo Comparator
Administered as a repeated SC doses in subjects with Type 1 Diabetes
干预措施: Placebo Comparator (Biological)
70 mg REMD-477
Experimental
Administered as a repeated SC doses in subjects with Type 1 Diabetes
干预措施: REMD-477 (Biological)
结局指标
主要结局
Change in Average Daily Total Insulin Use
时间窗: Baseline and 12 weeks
Change from Baseline in average daily total insulin use at Week 12
次要结局
- Seven-Point Glucose Profile - Change in Average 24-h Glucose Concentrations(Baseline and 12 weeks)
- Change in Hemoglobin A1c From Baseline at Week 13(Baseline and 13 weeks)
- Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hypoglycemia (Blood Glucose Range <70 mg/dL) at Week 12(Baseline and 12 weeks)
- Change From Baseline Difference in AUC Glucose Concentrations Following Mixed Meal Tolerance Test (MMTT) - Part A Only(Baseline and 13 weeks; AUC glucose timepoints: 10 minutes prior and just before (time ) initiating the mixed-meal ingestion and at 30, 60 and 120 minutes after the mixed meal ingestion.)
- Continuous Glucose Monitoring (CGM) - Change in Average Daily 24-hour Glucose Concentration at Week 12(Baseline and 12 weeks)
- Percentage of Subjects With HbA1c Reduction of ≥ 0.4% at Week 13(Baseline and 13 weeks)
- Change in Hemoglobin A1c at Week 13 in Subjects With Baseline HbA1c ≥7.5%(Baseline and 13 weeks)
- Change in C-peptide Adjusted AUC Following Mixed Meal Tolerance Test (MMTT)(Baseline and 13 weeks; AUC C-peptide timepoints: 10 minutes prior and just before (time 0) initiating the mixed-meal ingestion and at 30, 60 and 120 minutes after the mixed meal ingestion.)
- Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hyperglycemia (Blood Glucose Range >180 mg/dL) at Week 12(Baseline and 12 weeks)
- Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hypoglycemia (Blood Glucose Range <55 mg/dL) at Week 12(Baseline and 12 weeks)
- Summary of the Product of Average Daily 24-h Glucose Ratio and Daily Insulin Use Ratio (Day 78 [Week 12]/Baseline)(Baseline and week 12)
- Change in Baseline Difference in Glucagon Adjusted AUC Following Mixed Meal Tolerance Test (MMTT) - Part A Only(Baseline and 13 weeks; AUC glucagon timepoints: 10 minutes prior and just before (time ) initiating the mixed-meal ingestion and at 30, 60 and 120 minutes after the mixed meal ingestion.)
- Proportion of Subjects With Positive Anti-REMD-477 Antibodies(Day 1 (pre-dose), Day 85 (Week 13) and Day 162 (Week 24))
- Summary of REMD-477 Plasma Concentrations(Baseline (Day 1 pre-dose) and Weeks 2, 5, 9, 13 and 16.)
- Proportion of Subjects With Targeted Hemoglobin A1C (HbA1c) of ≤ 7.0% at Week 13(Baseline and 13 weeks)
- Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Target Blood Glucose Range (70-180 mg/dL) at Week 12(Baseline and 12 weeks)
研究者
研究点 (11)
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